The objective of the studies described in Part A of this proposal is to conduct Phase I, II, and III investigations of new modes of therapy for HIV infection as well as for opportunistic infections and malignancies. In the first year, 150 patients would be enrolled: 100 in Phase II/III studies, and 50 in Phase I studies. Phase I investigations would focus on antiretroviral therapy, although plans to conduct Phase I studies of Pneumocystis carinii pneumonia and/or human papillomavirus (HPV) infections are also discussed. Phase II/III studies would evaluate antiretroviral therapy and/or treatment or prophylaxis for opportunistic infections. Most neurologic studies would be "piggybacked" onto primary infection studies. Detailed plans are presented to increase community involvement in the ACTU, and to augment enrollment of women, minorities, substance abusers, and persons with hemophilia. In addition to Part A, this application includes six optional components. Part B proposes studies to evaluate new modes of HIV therapy in children. Components C.1 and C.2 propose to establish Virology and Pharmacology Core Laboratories, respectively. The objective of component C.3 is to utilize PCR methodology to quantitate HIV-1 DNA and RNA, analyze antiretroviral resistance, and increase sensitivity of HIV-1 culture systems, as well as to examine mechanisms of indeterminate western blot reactivities and the impact of co-infection with HTLV- I and/or II. The objective of component Cl4 is to establish a comprehensive, clinical and laboratory-based pharmacology program for evaluation of antiretroviral drugs. The objective of C.5 is to evaluate cytokines, circulating and produced in vitro, as potential surrogate markers for use in clinical studies. We propose to carry out these studies by maintaining the University of Rochester ACTU consortium, which consists of the University of Rochester, SUNY Buffalo, and SUNY Syracuse. The Principal Investigator is from the University of Rochester, which would continue to serve as the parent unit of the consortium. Immunophenotyping studies would be carried out at the University of Rochester. if components C.1 and C.2 are awarded, all virologic and pharmacologic studies would be conducted in Rochester and Buffalo, respectively. Procedures to ensure efficient operation of the consortium are well established.